Local C1q/TNF-related protein 1 attenuates kidney inflammation and fibrosis by regulating macrophage activation.

Abstract

Chronic kidney disease (CKD), characterized by persistent inflammation and progressive renal fibrosis, remains a major therapeutic challenge due to incomplete understanding of its pathogenesis. Since C1q/TNF-related protein 1 (CTRP1) plays a potential role in fibrosis and inflammation in other tissues, we investigated the role of CTRP1 in patients and mice with CKD. Here CTRP1 expression was increased in plasma and decreased in kidneys from patients with CKD. Upregulation of renal CTRP1 with adeno-associated-CTRP1 were associated with decreased renal fibrosis, inflammation, macrophage accumulation and activation in mice models. Mechanistically, CTRP1 abolished the expression of TGFß1-induced macrophage M2-associated genes and the transcriptional regulators Yes-associated protein Yap)/transcriptional coactivator with PDZ-binding motif (Taz). Additionally, upregulation of CTRP1 could partly down regulate LPS-stimulated expression of pro inflammatory genes in vitro. Conditioned media from TGFß1-CTRP1-pretreated macrophages could less efficiently stimulate fibroblast activation compared to those from TGFß1-pretreated macrophages. Thus, our study reveals local CTRP1 as a potential regulator of chronic inflammation and kidney fibrosis through regulating macrophage activation. Taking together, these findings support renal CTRP1 as a novel therapeutic target for CKD.